The corneal endothelium is a unique tissue of the body that is a monolayer of cells lining the back surface of the cornea of the eye. The status of the corneal endothelium of the eye is of primary importance in maintaining the normal transparency of the human cornea. As a result of trauma or disease this cell layer can malfunction and this can result in corneal blindness. Clinical specular microscopy, originally developed in this laboratory, provides a non-invasive clinical method to evaluate the corneal endothelium in normal and diseased corneas and to assist in the diagnosis and treatment of corneal disease. With specular microscopy a variety of changes whose interpretation is uncertain are seen in the corneal endothelium of patients having corneal endothelial problems. In addition, the mechanisms by which the corneal endothelium recovers from trauma are poorly understood. Only in the past year has our laboratory shown that human adult corneal endothelial cells can undergo coalescence and (presumably) cell division processes that were previously thought to be unlikely. In order to be better able to treat patients with corneal endothelial problems more information is needed concerning the nature of corneal endothelial wound healing. This proposal has the goals of developing efficient models for studying corneal endothelial wound healing, of determining the nature and mechanisms of corneal endothelial wound healing, and of determining the nature of the morphological changes that are seen by specular microscopy during healing of the corneal endothelium.